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OBJECTIVE: Fructose is partly metabolized in small bowel enterocytes, where it can be converted into glucose or fatty acids. It was therefore hypothesized that Roux-en-Y gastric bypass (RYGB) may significantly alter fructose metabolism. METHODS: We performed a randomized clinical study in eight patients 12-17 months after RYGB and eight control (Ctrl) subjects. Each participant was studied after ingestion of a protein and lipid meal (PL) and after ingestion of a protein+lipid+fructose+glucose meal labeled with (13) C-fructose (PLFG). Postprandial blood glucose, fructose, lactate, apolipoprotein B48 (apoB48), and triglyceride (TG) concentrations, (13) C-palmitate concentrations in chylomicron-TG and VLDL-TG, fructose oxidation ((13) CO2 production), and gluconeogenesis from fructose (GNGf) were measured over 6 hours. RESULTS: After ingestion of PLFG, postprandial plasma fructose, glucose, insulin, and lactate concentrations increased earlier and reached higher peak values in RYGB than in Ctrl. GNGf was 33% lower in RYGB than Ctrl (P = 0.041), while fructose oxidation was unchanged. Postprandial incremental areas under the curves for total TG and chylomicrons-TG were 72% and 91% lower in RYGB than Ctrl (P = 0.064 and P = 0.024, respectively). ApoB48 and (13) C-palmitate concentrations were not significantly different. CONCLUSIONS: Postprandial fructose metabolism was not grossly altered, but postprandial lipid concentrations were markedly decreased in subjects having had RYGB surgery.